An enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.

The immune response is essential for survival by destroying microorganisms and pre-cancerous cells. However, inflammation, one aspect of this response, can result in short- and long-term deleterious side-effects. Mclk1⁺/⁻ mutant mice can be long-lived despite displaying a hair-trigger inflammatory r...

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Autores principales:	Dantong Wang, Ying Wang, Catherine Argyriou, Audrey Carrière, Danielle Malo, Siegfried Hekimi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c4a37b066ebf4341844796b2c386072b
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spelling	oai:doaj.org-article:c4a37b066ebf4341844796b2c386072b2021-11-18T08:08:41ZAn enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.1932-620310.1371/journal.pone.0049606https://doaj.org/article/c4a37b066ebf4341844796b2c386072b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23166727/?tool=EBIhttps://doaj.org/toc/1932-6203The immune response is essential for survival by destroying microorganisms and pre-cancerous cells. However, inflammation, one aspect of this response, can result in short- and long-term deleterious side-effects. Mclk1⁺/⁻ mutant mice can be long-lived despite displaying a hair-trigger inflammatory response and chronically activated macrophages as a result of high mitochondrial ROS generation. Here we ask whether this phenotype is beneficial or simply tolerated. We used models of infection by Salmonella serovars and found that Mclk1⁺/⁻ mutants mount a stronger immune response, control bacterial proliferation better, and are resistant to cell and tissue damage resulting from the response, including fibrosis and types of oxidative damage that are considered to be biomarkers of aging. Moreover, these same types of tissue damage were found to be low in untreated 23 months-old mutants. We also examined the initiation of tumour growth after transplantation of mouse LLC1 carcinoma cells into Mclk1⁺/⁻ mutants, as well as during spontaneous tumorigenesis in Mclk1⁺/⁻Trp53⁺/⁻ double mutants. Tumour latency was increased by the Mclk1⁺/⁻ genotype in both models. Furthermore, we used the transplantation model to show that splenic CD8⁺ T lymphocytes from Mclk1⁺/⁻ graft recipients show enhanced cytotoxicity against LLC1 cells in vitro. Mclk1⁺/⁻ mutants thus display an association of an enhanced immune response with partial protection from age-dependent processes and from pathologies similar to those that are found with increased frequency during the aging process. This suggests that the immune phenotype of these mutants might contribute to their longevity. We discuss how these findings suggest a broader view of how the immune response might impact the aging process.Dantong WangYing WangCatherine ArgyriouAudrey CarrièreDanielle MaloSiegfried HekimiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49606 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dantong Wang Ying Wang Catherine Argyriou Audrey Carrière Danielle Malo Siegfried Hekimi An enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.
description	The immune response is essential for survival by destroying microorganisms and pre-cancerous cells. However, inflammation, one aspect of this response, can result in short- and long-term deleterious side-effects. Mclk1⁺/⁻ mutant mice can be long-lived despite displaying a hair-trigger inflammatory response and chronically activated macrophages as a result of high mitochondrial ROS generation. Here we ask whether this phenotype is beneficial or simply tolerated. We used models of infection by Salmonella serovars and found that Mclk1⁺/⁻ mutants mount a stronger immune response, control bacterial proliferation better, and are resistant to cell and tissue damage resulting from the response, including fibrosis and types of oxidative damage that are considered to be biomarkers of aging. Moreover, these same types of tissue damage were found to be low in untreated 23 months-old mutants. We also examined the initiation of tumour growth after transplantation of mouse LLC1 carcinoma cells into Mclk1⁺/⁻ mutants, as well as during spontaneous tumorigenesis in Mclk1⁺/⁻Trp53⁺/⁻ double mutants. Tumour latency was increased by the Mclk1⁺/⁻ genotype in both models. Furthermore, we used the transplantation model to show that splenic CD8⁺ T lymphocytes from Mclk1⁺/⁻ graft recipients show enhanced cytotoxicity against LLC1 cells in vitro. Mclk1⁺/⁻ mutants thus display an association of an enhanced immune response with partial protection from age-dependent processes and from pathologies similar to those that are found with increased frequency during the aging process. This suggests that the immune phenotype of these mutants might contribute to their longevity. We discuss how these findings suggest a broader view of how the immune response might impact the aging process.
format	article
author	Dantong Wang Ying Wang Catherine Argyriou Audrey Carrière Danielle Malo Siegfried Hekimi
author_facet	Dantong Wang Ying Wang Catherine Argyriou Audrey Carrière Danielle Malo Siegfried Hekimi
author_sort	Dantong Wang
title	An enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.
title_short	An enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.
title_full	An enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.
title_fullStr	An enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.
title_full_unstemmed	An enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.
title_sort	enhanced immune response of mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c4a37b066ebf4341844796b2c386072b
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An enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging.

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